Nuclear magnetic resonance (NMR) spectrometers first became available in 1946. In 1950 observations of "shifted" resonances in nitrogen spectra by W. G. Proctor & F. C. Yu, Phys. Rev. 77, 717, (1950) stimulated efforts to improve the homogeneity and stability of magnets used in the experiments and led to the observation of chemically shifted resonances in proton spectra by J. T. Arnold, S. S. Dharmatti, and M. E. Packard, Jour. Chem. Phys. 19, 1608, (1951). This marked the beginning of high resolution NMR and its application as an analytical tool for chemistry, and sparked rapid growth in the development of NMR spectrometers. This development continues today at a pace limited only by the availability of relevant technology. Recent work is predicated upon improvements in rf probe performance incorporating receiver coils made from recently available high temperature superconducting (HTS) materials.
Nuclei of most isotopes of the elements have non-zero spin and exhibit gyromagnetic properties. They behave like microscopic spinning bar magnets and possess a coupled nuclear magnetic moment. In the absence of an externally applied magnetic field the nuclear moments of an ensemble of non-zero spin nuclei are randomly oriented in their atomic or molecular environment. When a static homogeneous magnetic field B is applied, the magnetic moments interact with the field and become oriented with respect to it. The spins are then said to be "polarized" by the field. Only certain orientations are allowed in accordance with well known quantum mechanical principles as described in "Nuclear Magnetic Resonance--Principles and Theory", R Kitamaru, eds. Elsevier Science Publishers, 1990, Chap 2, pp. 25-36. As a consequence of the interaction of the field with the nuclear spin system, the nuclear energy level splits into multiple discrete levels corresponding to the different allowed orientations. Nuclei with spin equal 1/2 are the most suitable and most frequently used for high resolution NMR experiments. For simplicity and without loss of generality with respect to this present work, spin equal 1/2 nuclei will be assumed hereinafter. The split into two energy levels, corresponds to magnetic quantum numbers +1/2 and -1/2 for a spin 1/2 nucleus. The separation of the energy levels is proportional to the intensity of the magnetic field at the nucleus and to a proportionality constant .gamma. called the magnetogyric ratio. In thermal equilibrium in the static field, a Boltzmann distribution of energies is maintained. There are more spins in the lower energy state than in the higher energy state. This difference is called the Boltzmann excess.
When an ensemble of nuclei are simultaneously subjected to both a static magnetic field and an appropriate rf magnetic field of frequency .nu. such that the energy of a quantum of radiation h.nu., where h is Planck's constant, is equal to the energy difference between the two spin energy levels, transitions can occur with equal probability from one state to the other. Due to the Boltzmann excess there is a net absorption of energy by the nucleus from the rf field. This transfer of energy is a necessary condition for obtaining a NMR signal.
In the aggregate, large ensembles of nuclei such as would be present in practical size samples obey the laws of classical dynamics. For convenience of visualization and ease of understanding, a classical vector model of the NMR phenomenon is hereinafter described.
With the static magnetic field applied, individual nuclei align themselves to the field, some with their microscopic magnetization vector substantially in the direction of the field, which is the low energy state corresponding to spin equal +1/2. Also, some nuclei align with their magnetization vector substantially in the direction opposite to the field, which is the high energy state corresponding to spin equal -1/2. In accordance with the Larmour Precession Theorem the individual nuclei precess about the direction of the field with an angular frequency .omega..sub.L =.gamma.B, where .gamma. is the aforementioned magnetogyric ratio for each of the isotopic species, and B is the local field at the nuclei. More nuclei align in the direction of the field than in the direction opposite to the field, the difference being equal to the Boltzmann excess. Therefore, collectively the ensemble of nuclei exhibits a net macroscopic nuclear magnetization vector in the direction of the applied polarizing field B.
To generate a NMR signal, rf excitation is applied to the sample by a rotating magnetic field in the plane perpendicular to the direction of the polarizing field thereby enabling a transfer of energy to the spin system. The rotating field is provided by an alternating current in an excitation coil having its axis of symmetry perpendicular to the direction of the polarizing field. A linear oscillating magnetic field is generated along the x- axis of the excitation coil as shown in FIG. 1a. The linear oscillating field can be decomposed into two counterrotating components, one of which, usually called the B.sub.1 field, rotates in the direction of rotation of the aforementioned ensemble of nuclear spins, as shown in FIG. 1b. When the angular frequency .omega. of the two rotating magnetic field components 20 and 22 is equal to .omega..sub.L, the angular frequency of precession of the ensemble of nuclei 23, a resonance condition exists and, as shown in FIG. 1c, the net magnetization vector 8 tilts away from the z-axis 24 which is the direction of the static polarizing field 12 and precesses about it. As the magnetization vector 8 precesses about the polarizing field, it intersects the turns of a receiver coil, thereby generating a NMR signal. At resonance the angular frequency .omega. in the vector description equals 2.pi..nu., where .nu. is the frequency of excitation which produces transitions between spin states in the quantum description of the phenomenon.
The broad general utility of NMR as a tool for determining the chemical structure of compounds is due to the influence of the molecular environment on the local magnetic field at the nuclei. The local magnetic field at the nucleus of a particular nuclear species at a particular site in a molecule is the vector addition of the externally applied field, altered slightly by the magnetic influence of its molecular environment. By way of example, circulation of electrons about the nucleus caused by the applied field results in an induced field at the nucleus which in some instances opposes the applied field (diamagnetism), and in some instances augments it (paramagnetism). By way of further example the local field at the nucleus can be additionally modified, taking on multiple values or "splitting" due to interactions with other non-zero spin nuclei in the molecule. As discussed hereinafter, these two effects, known as "chemical shift" and "spin-spin coupling" respectively are major sources of the fine structure seen in NMR spectra as described in "Introduction To NMR Spectroscopy", R. Abrahms.; J Fisher, P. Loftus, pubs. J Wiley & Sons, 1993, chap. 2, pp. 13-33, chap. 3, pp. 34-53. NMR spectra which are characterized by resonance lines that are narrower than the shifts in resonance caused by chemical shift and spin-spin coupling are known as high resolution spectra and are primarily made possible by the application of an extremely homogeneous polarizing field.
An NMR spectrometer is comprised of: 1) a D.C. magnet which provides said stable homogeneous magnetic field for polarizing the spins, 2) an rf system which provides a suitable rf excitation signal, 3) a coil or a plurality of coils for coupling the rf excitation to the spins and for receiving the NMR response signal, 4) a detection system for detecting the NMR response signal, 5) a signal processing system for processing the detected NMR response signal, and 6) an output device for displaying the NMR signal. For high resolution NMR studies, the compound under investigation is usually dissolved in or mixed with a suitable solvent and is in liquid form contained in a sample tube which is typically 5 mm in diameter. The sample is held in a sample holder portion of a probe which positions it in the most homogeneous region in the magnetic field. The coil or coils for coupling the rf excitation to the sample and for detecting the NMR signal are mounted on the probe.
NMR is an inherently insensitive technique. Sensitivity is strictly defined in terms of the minimum concentration of a test material required to produce a signal that is just detectable above the level of noise. For practical purposes however, the signal to noise ratio, S/N, is generally considered a good measure of sensitivity and the terms sensitivity and S/N ratio will be used interchangeably hereinafter.
The NMR signal is small for two fundamental reasons and numerous practical considerations. The first fundamental reason is that the energy changes involved in NMR transitions are small, and the second is that the net absorption of energy by an ensemble of nuclei is proportional to only the excess in population of the lower of the two energy states involved in the transition (i.e. the Boltzmann excess), rather than the total population. Specifically, the ratio of the number of spins in the higher energy state to the number in the lower energy state is (1-h.nu./kT) where k is the Boltzmann constant. Therefore this excess population is very small, a typical value being of the order of 1 part in 10.sup.5. Other reasons for the small signal include the need to use dilute solutions of the species being observed, either because of limited availability of sample material or to prevent spectra being complicated and rendered unreproducible by the effects of intermolecular coupling.
As further discussed hereinafter, the dominant source of noise which enters into the determination of sensitivity is generally thermal noise originating in the receiver coil of the spectrometer.
In early continuous wave (CW) spectrometers, sample resonances were excited one at a time by a continuous sweep of the rf excitation or static magnetic field.
In modern NMR spectrometers one or more high intensity rf excitation pulses of short duration are applied and the NMR response of the spin system to the excitation is received and recorded as the spin system relaxes back towards its equilibrium state. The receiver is off during the excitation pulse. Then when the transmitter is switched off, the receiver is switched on to record the NMR response. Since one is off when the other is on, the excitation and receive functions can time share the same coil. Alternately, separate coils can be used for excitation and reception. When the rf excitation is removed the magnetization vector relaxes and precesses about the static field. As it precesses and intersects the turns of the receiver coil, an NMR time domain response signal called a Free Induction Decay, FID, is generated. The terminology "Free Induction Decay" derives from the characterization of the signal as being induced by a magnetization vector "free" of the influence of the rf excitation, while it is "decaying" back to equilibrium. The time domain FID signal is then converted to a frequency domain spectrum, by means of a Fourier Transformation. Instruments operating in this manner are called Pulsed FT NMR Spectrometers.
In a pulsed FT spectrometer all frequencies in the spectral band of interest are excited simultaneously and the resulting FID, when Fourier transformed, yields a spectrum over the entire band of interest. The time for acquiring data in a pulsed spectrometer is therefore greatly reduced and as a consequence, time averaging of FID's from multiple scans can be done in a reasonable time prior to Fourier transformation of the data. This results in an improvement in the signal to noise ratio, S/N, on the order of the square root of the number of scans. Time averaging is one of many methods and techniques that are routinely used to improve the sensitivity of NMR spectrometers.
Continued improvement in sensitivity has been a constant objective in the development of NMR spectrometers. Increasing signal strength, reducing noise, and improving signal processing methods have all contributed. Many of the factors that influence the attainable signal to noise ratio are treated in "A Handbook of Nuclear Magnetic Resonance ", R. Freeman, pubs, Longman Scientific & Technical, 1988, pp. 216-229 which is hereby incorporated herein by reference. As discussed hereinafter, the signal to noise ratio can be further improved by cooling the receiver coil to a very low temperature while maintaining the sample at or near room temperature to reduce Johnson noise.
The available signal is proportional to both the nuclear magnetization and to the resonance frequency. Since the nuclear magnetization is proportional to the resonance frequency, the available signal for a given species is proportional to the square of the resonance frequency. Noise considerations however reduce the dependence of sensitivity on the resonance frequency to .omega..sup.3/2 Largely because of this strong dependence of sensitivity on frequency, the trend has been toward higher and higher magnetic field strength and correspondingly higher values of NMR frequencies. Most modern NMR spectrometers utilize superconducting magnets capable of providing fields as intense as 18 tesla which are homogeneous over suitable sample size volumes. 17.6 tesla corresponds to an NMR frequency of 750 Mhz for protons.
Most modern NMR spectrometers have three separate transmitter channels: one to provide for a conventional field-frequency lock system, a second to provide the signal for observing the nucleus under study, and a third to provide 2D and decoupling capability. A block diagram of a typical modern pulsed spectrometer is shown in FIG. 2.
The probe is a critical component in an NMR spectrometer. For a given static magnetic field strength and a given sample size, the performance of the probe defines the sensitivity of the spectrometer. An important consideration in probe design is the coupling efficiency .zeta. of the receiver coil to the sample. .zeta. is the ratio of effective inductance to total inductance of the receiver coil. Any portion of the inductance of the receiver coil that does not contribute towards the detection of the NMR signal, such as coil leads by way of example, results in a loss of sensitivity proportional to .zeta..sup.1/2. Another important consideration is the quality factor Q of the receiver coil which affects sensitivity by a factor of Q.sup.1/2 since signal voltage is proportional to Q and noise voltage is proportional to Q.sup.1/2. Q represents the ratio of energy stored in the receiver coil resonant circuit to the energy dissipated through resistive losses in the circuit. Another important consideration in probe design is the receiver-coil filling factor .xi. which, for a fixed coil- volume, influences the signal strength and the sensitivity directly. In the simple case of a cylindrical coil with diameter d.sub.c wrapped around a cylindrical sample with diameter d.sub.s, .xi. would be approximately (d.sub.s /d.sub.c).sup.2. .xi. is a measure of the energy stored in the transverse magnetic field coupling to the sample, compared to the total magnetic energy stored in the receiver coil resonant circuit. Filling factor .xi., coupling efficiency .zeta., and quality factor Q should all be as large as possible for maximum sensitivity.
In many cases it is desirable, to simultaneously irradiate an NMR sample with several rf fields, each with a different frequency, without strong interaction occurring between the circuits producing the irradiating fields and the circuits detecting the responses. It is known in the art that transmitter drive can be largely decoupled from receiver coils by positioning the transmitter and the receiver coils on the probe at right angles to each other. This so called quadrature-coil configuration minimizes flux coupling between the coils. By making the mutual inductance between the coils very small the coupling of the strong irradiating signal to the sensitive receiver circuit can be largely eliminated.
Modern spectrometers use superconducting magnets. The cylindrical sample is positioned coaxially with the D.C. magnet. The transmitter and receiver coils can be a saddle coil as shown in FIG. 3a or a split formed-wire coil as shown in FIG. 3b. Either are ordinarily shaped to couple closely to the sample while providing the required B.sub.1 field orthogonal to the static field B. Using high temperature superconducting (ITS) materials, coils have been fabricated by depositing a thin layer of superconductor on a flat dielectric substrate 45. A pair of such coils forming a magnetically coupled system, a Helmholtz pair, are shown in FIG. 4a, placed on opposite sides of a sample is in the prior art. Also in the prior art, a second pair of similar HTS coils is shown positioned orthogonal to the first pair as shown in FIG. 4b to simultaneously provide a field-frequency lock signal. HTS coils can have high currents induced therein which can drive the coil normal and destroy the Q or significantly reduce the Q resulting in loss of detection sensitivity.
Best results are obtained with HTS coils when the superconductor is lattice matched to the substrate, i.e. grown epitaxially. The substrate 45 should be a thermally conductive material to facilitate cooling of the coil and should have low magnetic susceptibility to avoid degrading the homogeneity of the magnetic field. Acceptable substrate materials include sapphire, lanthanum aluminate, and magnesium oxide. A preferred HTS material is YBa.sub.2 Cu.sub.3 O.sub.7-.delta. (YBCO), which has a critical transition temperature T.sub.c of approximately 87.degree. K. A coil made of this material is described in "HTS Receiver Coils For Magnetic Resonance Instruments", R. S. Withers, B. F. Cole, M E. Johansson, G. C. Liang, G. Zaharchuk, Proc. SPIE, 2156, 27-35, (1994).
For proper performance HTS coils must be maintained at a temperature significantly below their transition temperature T.sub.c. Joule-Thomson and Gifford-McMahon closed cycle refrigerators are known which cool the coils to 25.degree. K. The coils are thermally isolated from the samples in this equipment and the samples can be maintained at or near room temperature if desired.
High resolution NMR probes using HTS coils can provide higher sensitivity than probes with non-superconducting coils. For a given sample volume the sensitivity of a coil is proportional to (.xi.Q/T).sup.1/2 where T is the coil temperature and .xi. and Q are the aforementioned filling factor and quality factor respectively. A superconducting coil may have a Q of 20,000 compared with 250 for a room temperature coil and can operate at 25.degree. K. With the geometry appropriate for a 5 mm. sample tube, and allowing for the loss of filling factor required for thermal isolation of the sample from the coil, the potential sensitivity gain can approach a factor of 10.
Any of the aforementioned coil configurations can be used to provide excitation and to detect NMR responses at more than one frequency by tuning the probe coil circuit to resonate at more than one frequency. However, since inductive elements are used to provide the frequency separation, multiple tuning degrades performance of the probe compared to a single tuned probe because of the inevitable reduction in the aforementioned coupling coefficient .zeta.. Combining the use of multiple tuning of probe coil circuits and orthogonal coil disposition, any of the aforementioned prior art probe arrangements can provide rf excitation and reception of NMR responses at several different frequencies. Disadvantages of the prior art probe when used in this way include the aforementioned reduction in sensitivity due to lower coupling coefficient as well as high cost of fabrication. Additionally it is difficult to perform adjustments to minimize mutual coupling between orthogonal pairs.